Film-Forming Resins as a Carrier for Topical Application of Pharmacologically Active Agents

ABSTRACT

The invention provides a biological dressing for treatment of a dermatological disease comprised of one or more resins or other film-forming agents, a topically acceptable volatile solvent, and a pharmacologically active agent. The combined one or more resins are present in a suitable amount such that the composition, when the solvent evaporates, will dry to form a solid coating that sticks to the skin, nail or mucosal membrane to which the composition is applied, and maintain the pharmacologically active agent over a sustained period of time in contact with sites on the skin or mucosal membranes exhibiting symptoms of the disease. Methods are provided for treating symptoms of dermatological diseases with such a pharmacological composition.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The invention relates to resin or other film-forming agent basedbiological dressings that adhere to the skin and contain one or morepharmacologically active agents for the treatment of symptoms relatingto dermatological diseases and those affecting mucous membranes. Theinvention is exemplified by biological dressings comprising tincture ofbenzoin and clotrimazole for the treatment of athlete's foot and bybiological dressings comprising mastic and ciclopirox for onychomycosis.

2. Background Information

For many forms of dermatological conditions, the powders, sprays,solutions, lotions and creams available over-the-counter lackeffectiveness. The reason for this varies, from poor delivery of themedication to the source or cause of the condition, to loss of themedication through abrasion from normal activity of the patient, toabsorption of medications applied to the skin by the patient's socks orclothes. For these various reasons, currently available commercialmedications are prone to come off easily once applied to the affectedarea, and consequently much of the medication is wasted, either throughover application in an attempt to anticipate the problem, or in medicinequickly being dispersed away from the site. The medications for theseconditions typically require at least 2 to 4 weeks of continuoustreatment, and thus often fail due to this poor delivery.

A further problem with the use of existent medications is the lack ofcompliance by patients. Due to the mess and difficulty of use, patientswill often use these over the counter medications only until theirsymptoms abate and then they will stop the medication, before therecommended course of treatment is completed, and hence often before theinfection has truly cleared. Though momentarily abated, the infectionthen begins to take hold again, and in a matter of days or weeks a fullblown infection occurs again. In many cases the patient will repeatusing the over the counter medication until the symptoms clear, andagain stop the medication with the first sign of abatement, with thewhole cycle repeating.

Hence, there is a need for a clean and inexpensive vehicle/carrier oftopically applied medications that increases the convenience andeffectiveness of the treatment and decreases the necessary time for thetreatment. It is preferably associated with less waste and lower cost,and ultimately leads to improved treatment of patient symptoms andincreased patient satisfaction.

In medicine, tincture of benzoin and mastic gum (Mastisol) have beenemployed to form a sticky coating on skin prior to the placement ofadhesive preparations. Tincture of benzoin has also been used to form abiologic dressing over superficial cutaneous wounds as well as aphthousulcers (canker sores). However, the general use of resins, such asmastic and benzoin gum, as semi-permanently applied carriers forincreasing the efficacy and usefulness of topological of pharmacologicalagents has not been disclosed.

A tincture of benzoin has been used with podophyllin resin (10-25%) inthe treatment of genital warts. It is considered by many to becumbersome and inconvenient (see U.S. Pat. Nos. 5,063,065 and5,167,649). Unfortunately, podophyllin resin is toxic, and even whenapplied in a tincture of benzoin, this agent must be removed by rigorouswashing 1 to 6 hours post-application. Due to the problems associatedwith using podophyllin resin in tincture of benzoin, other carriers havebeen sought. As an example, in the treatment of genital warts, Goh, etal. (Singapore Med J (1998) 39:17-19) reports that podophyllin preparedin 0.25% ethanol can be self-applied and is as efficacious aspodophyllin prepared in tincture of benzoin and applied in the clinic.Use of tincture of benzoin as a biological bandage with compounds thatit is desirable to have in long contact with the skin has not beenreported.

SUMMARY OF THE INVENTION

Compositions and methods are provided for increasing the effectivenessof treatment of dermatological disorders on the skin or a mucousmembrane of a mammal by using a resin or other film-forming agent as acarrier for a pharmacologically active agent. The pharmacologicalcompositions are comprised of one or more resins or other film-formingagents, at least one topically acceptable pharmacologically active agentfor treatment of a dermatological disorder other than the resins orother film-forming agents, wherein the active agent is non-toxic to themammal being treated when left in contact with the lesion of interestfor greater than four hours, and a topically acceptable volatilesolvent. The compositions optionally can include a penetration enhancer.The methods of treating symptoms of a dermatological disorder includethe steps of contacting affected sites on the skin or nails of a patientin need thereof with the pharmacological composition comprised of one ormore resins or other film-forming agents, a pharmacological agent oragents, and an evaporative solvent, and allowing it to dry to form aresin-based biological dressing. The biological dressing comprises asticky film of the one or more resins or other agents which form a filmon the skin and a pharmacologically active agent; the latter remains onthe skin, nail or mucous membrane after the volatile solvent hasevaporated from the one or more resins or other film-formingcomposition. The dressing forms a hydrophobic, protective film thatprovides sustained release of the pharmacologically active agent at thesite of application. The invention finds use in the treatment ofdermatological disorders such as infection, inflammation, andhyperproliferation of epidermal cells.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graphical representation showing data from a skinpenetration study of a composition of the invention.

FIG. 2 is a graphical representation showing in vitro franz cellpenetration results.

DETAILED DESCRIPTION OF THE INVENTION

Compositions and methods are provided for the convenient and effectivetreatment of at least one symptom of a dermatological disorders in amammal, particularly a human, in need thereof, with a biologicaldressing. By “biological dressing” or “biologic dressing” or “biologicbandage” is intended a non-occlusive but adherent pharmacologicalcomposition that is formed by drying on the skin a pharmacologiccomposition comprised of one or more resins, such as benzoin, mastic orother compositions that can form a barrier film on the skin, such ascompositions that are used as skin wound sealing agents, one or morepharmacologically active agents and a topically acceptable volatilesolvent, such as ethanol. The resin-based biologic dressing forms aprotective coating at the site(s) on the skin, nails or mucosal membraneexhibiting symptoms of the disorder and also acts as a reservoir for thepharmacologically active agent(s) to provide sustained delivery of anappropriate medication or combination of medications to the site.

The skin disorder symptoms to be treated include, but are not limitedto, skin, nail and mucosal membrane lesions, inflammation, itching,scaling and pain. The disorders include viral, fungal and bacterialinfections, inflammatory conditions, and hyperproliferative disorders.The pharmacological agent(s) can include topically active agents thatcan be used to ameliorate skin disorder symptoms, includingantimicrobial and antiviral agents, anti-inflammatory agents, analgesicsand anesthetics. As desired, the effectiveness of the pharmacologicalagent(s) optionally can be increased by including a skin or nailpenetration enhancer in the pharmacologic composition.

The biological bandage is easily removed using a solvent such asethanol. Since the coating that contains the medication stays in placeuntil such deliberate removal, the effectiveness of the treatment isincreased since the skin is exposed to the active ingredient for alonger period of time. This also allows for a decreased treatment time,and, ultimately, improved treatment of symptoms and increased patientsatisfaction. Thus, compositions of the invention can be used to improvedelivery of medications that are soluble in organic solvents such asalcohols that are typically applied topically for the treatmentdermatologic disorders. The advantages of the subject invention includea more specifically directed application of medications to sitesaffected by a skin disorder, and extended retention on the skin of themedication because the film is resistant to water and abrasion byclothing. Additionally, the vehicle is relatively inexpensive, ispleasant smelling, and the bandage can be conveniently and easilyremoved, for example with alcohol, when desired. Many dermatologicalconditions are exacerbated by moisture so the water repellent qualitiesof the dressing also protect the skin from further damage. Theresin-based biological dressings of the invention are designed to bedirectly applied to a lesion needing treatment, and left in place for anextended period of time, without requiring conventional adhesivebandages. It is intended that the dressing need only be washed from thelesion for purposes of convenience and cleanliness. The biologicaldressings of the subject invention are cleaner and easier to apply thanconventional dressings and existing medications, have less waste and aremore economical, allowing for more efficient, efficacious and palatablerelief of symptoms or recovery from the skin disorder being treated.Overall treatment success is increased by decreasing the time requiredfor therapy, for example for athlete's foot, from about four weeks toseven to ten days while decreasing the total amount of medication neededand improving patient compliance.

Further advantages of the subject invention include that various of theresins that find use, including benzoin and mastisol, and wound sealingagents are already approved for human use and have been tested and foundto be safe for topical application on non-human mammals; the woundsealing agents have the advantage of being able to deliveralcohol-insoluble medications while reducing pain during application toan open wound.

The resin-based biological dressings are prepared by drying on the skin,a pharmacological composition comprising an agent that can be used toameliorate the symptoms of a dermatological disease and one or moreresins dissolved in a volatile solvent. Generally, the pharmacologicalcomposition is prepared as a sticky slurry or solution of the combinedone or more resins or film-forming agents and the pharmacologicallyactive agent that can be applied to a site on the skin or a mucosalmembrane. The consistency of the pharmacological composition can bevaried by adjusting the ratio of solvent to the combined one or moreresins in the composition to achieve the desired consistency forapplication to a particular site. For areas where evaporation of solventmay be slower, for example, application to lesions on a mucosal membranesuch as the gums, it may be desirable to prepare the composition as apaste and to use a more volatile solvent, whereas for application tohard to reach areas, such as between the toes, it may be desirable toprepare a less viscous composition that can be applied thinly to theaffected areas. However, for treatment of more severe lesions innon-visible areas, due to an athlete's foot infection for example,application of a more viscous preparation may be preferred. It should beunderstood that some wound sealing agents develop into a dry adhesivelayer or film once in contact with tissue, and therefore do notgenerally require use of a solvent other than what may be necessary toproperly blend in the pharmacologically active agent.

The relative proportions of the one or more resins or other film-formingagents, the pharmacologically active agent or agents and the evaporativesolvent in the preferred composition can vary widely, and depend uponthe specific intended use of the biological dressing. Precise preferredratios depend to some extent on the rate of release of thepharmacologically active agent from the film, the desired stickiness ofthe residual film, and the area of application. For example, if theintended application is to an affected area on the face, the preferredcomposition would have a lower proportion of combined resins or otherfilm-forming agents, to allow for a more thinly applied, less visibleand less sticky medical dressing. Generally, the pharmacologicalcompositions of the subject invention will typically have about 5% to90% resin or other film-forming agent, more likely about 20% to 85%, 30%to 70% or 40% to 60% resin or other film-forming agent. In oneembodiment, the pharmacological compositions will have about 1% to 15%resin or other film-forming agent.

The resin-based biological dressings of the invention may also becomprised of a combination of multiple resins or other film-formingagents, provided that when a non-resin film-forming agent is used incombination with a resin, the resin is the primary matrix of thecomposition. In one embodiment, the compositions of the subjectinvention will comprise a combination of one or more resins, each resinbeing less than 20% of the total composition. In some embodiments, thetotal concentration of the combined resins in the compositions of theinvention will exceed 20%, and may be as much as 20% to 90% of the totalcomposition. In other embodiments, the total concentration of thecombined resins may not exceed 20%, and may be as little as 1% to 20% ofthe total composition. Accordingly, the concentrations of each of theresins or other film forming agents may vary so long as toxicity to thesubject is avoided.

The stickiness of the biological dressings is provided by the use of acombination of one or more resins or other film-forming agents. Theresins that are useful in the methods and compositions of the inventioninclude, but are not limited to, naturally occurring resins and gums,such as those that are harvested from trees, although gum resins alsomay be prepared by synthetic means (see for example, U.S. Pat. Nos.5,644,049, 5,429,590 and 4,307,717). Exemplary resins include benzoinresinous exudate harvested from Styracaceae trees, including BenzoinSiam from Styrax Tonkinesis and Benzoin Sumatra from Styrax Benizoin.Tincture of benzoin and benzoin compound tincture is readily availablethrough numerous commercial sources, including many drug stores andsuppliers of surgical goods. Another resinous tree exudate that ispreferred and is commonly used in the medical arts for enhancing theadherence of surgical bandages, is mastic, a hard resin that isharvested from Pistacia lentiscus. A tincture of mastic gum (Mastisol)is produced by Ferndale Laboratories in Ferndale, Mich. and is alsoavailable through suppliers of surgical goods. Other resins that can beused include the gum resin exudates from Burserceae trees, includingBoswellia serrata (also known as Boswellin), Boswellia dalzielli,Boswellia carteri (olibanum gum) and the oleoresin Canarium luzonicum orCanarium commune (Elemi gum or resin). Oleoresins useful in thecompositions of the invention include balsam resins. Additional resinousexudates contemplated from other tree species include Eucalyptus species(Eucalyptus globulus) and Myrtaceae “Tea-tree” species (Melaleucaalternifolia, Leptospermum scoparium, and Kunzea ericoides). Manynaturally occurring resins themselves have pharmacological properties,and their topical application may cause irritation in certain patientsor exacerbate certain conditions. Prudent choice of the resins to beused in preparing a particular biological dressing takes intoconsideration the disorder to be treated and the sensitivities of aparticular patient's skin.

In addition to the resins discussed herein, biologic dressings can bemade from several classes of adhesive polymers including acrylicpolymers (e.g. cyanoacrylates), polyisobutylenes and silicones. Examplesof the acrylic polymers include acrylate-vinylacrylate,dimethylaminoethylmethacrylate, methacrylic esters,N-2-butylcyanoacrylate, 2-octylcyanoacrylate, polyacrylic acid,polyaminomethylmethacrylate and polymethylmethacrylate. Polyisobutylenes(a sub-type of polyolefins) are pressure sensitive adhesives made byblending multiple molecular weights to achieve desired adhesive anddrug-carrier properties. Silicones are available in the form of gels,liquids, or elastomers, depending on the nature of side groups and theinterchain cross-linking. Other potential adhesive vehicles includehydrogel polymers such as poly (oxypropylene-co-oxyethene) glycol,cellulose bioadhesives such as hydroxypropylmethyl-cellulose, syntheticlaticies such as polyvinyl acetate and ethylene vinyl-acetate, mucosaladhesives such as polyoxyethylene, pyroxylin solutions, and theiodophors. Commercial sources of film-forming agents that can becombined directly with a pharmacologically active agent includeDermabond (Ethicon) which is a formulation of 2-octylcyanoacrylate;Liquid Band Aid (Johnson and Johnson) which is also a formulation of2-octylcyanoacrylate; Liquiderm, Soothe-N-Seal, Nexa Band (all fromClosure Medical Co), all formulations of cyanoacrylate; “New-Skin” (NewSkin) containing pyroxylin; and hydrogels containing poly(oxypropylene-co-oxyethene) glycol (MedLogic).

A desirable feature of the subject compositions is that they form anadherent and protective film or biological bandage over a dermatologiclesion. To effect this attribute, the pharmacological composition isprepared with a volatile solvent that evaporates to leave a hydrophobiccoating comprised of the one or more resins or other film-forming agentsand the pharmacological agent on the skin or nail. Volatile solvents foruse in the subject compositions include ethyl acetate, n-propyl acetate,alcohols such as methanol, ethanol, propanol, and isopropanol, ketones,such as acetone, and ethers such as dimethyl ether. Other evaporativecompounds may also find use, so long as they are compatible with othercomponents of the pharmacological composition and topically acceptableto the majority of patients. The resins of choice are diluted in thevolatile solvent such that the concentration of solvent comprises about40% to 98% (v/v or v/w), more commonly at least about 50% to 95%, 65% to90%, 70% to 85%, preferably about 90% to 95% of the total composition.An exemplary composition contains a tincture of benzoin, which iscomprised of benzoin in about 75% to 83% ethanol.

The pharmacological agent or agents included in the pharmacologicalcompositions will depend upon the dermatological disorder being treated.To allow for extended contact of the biological dressing with the lesionunder treatment, pharmacological agents chosen should be efficaciouswithout being locally or systemically toxic or caustic to the mammal towhich the medicated dressing is administered. A biological dressing ofthe subject invention is intended to remain at the site of applicationfor greater than four hours, more often as long as 8, 10 or 12 hours,sometimes as long as 16, 18 or 20 hours, and for certain treatments, aslong as 24, 36 or 72 hours or even longer prior to removal. The time oftreatment desired is based at least in part upon the nature of thecondition to be treated and the pharmacological agent(s) that are beingused. In general, the pharmacological compositions are formulated sothat the concentration of the pharmacological agent(s) that is in thebiological bandage approximates the concentration of agent that is usedin existing topical formulations. However, because the adherentproperties of a film-forming resin-based biological dressing allow forextended and continuous exposure of a skin lesion to drug, reducedconcentration formulations are possible and in some cases preferred. Theamount to be used can therefore be adjusted as appropriate. Generally,the amount used will be within the range of ±25% of the indicatedconcentration, preferably within ±10% of the indicated concentrations.In the following paragraphs, the percentages appearing in parenthesisafter the name of a particular agent represent the concentration(s) ofagent that is (are) used in existing topical formulations.

The subject biological dressings find particular use in treatingnumerous dermatological disorders, including superficial infections(fungal, bacterial, viral and parasitic), and inflammatory skindisorders. As used herein, the term “skin” refers to the membranoustissue forming the external covering or integument of an animal andconsisting in vertebrates of the epidermis and dermis. As used herein,the term “nail” refers to a substructure, composed mainly of the proteinkeratin, of the outer layer of the skin. As such, “nail” includes both“fingernails” and “toenails” of an animal. The “nail bed” is the skin onthe top of which the nail grows. Additional uses include sustaineddelivery of pharmacological agents for hair growth stimulation and hairgrowth retardation, skin pigmenting and pigmentation removal agents,sunscreens, insect repellents, anti-anginal, anti-perspirant andanti-nausea agents.

Superficial fungal infections treatable by the subject compositionsinclude those caused by mold-like fungi (dermatophytes or tinea) oryeast-like fungi (Candida) that are confined to the stratum corneum orsquamous mucosa. Particularly considered is the treatment of tineainfections including onychomycosis (tinea unguium), athlete's foot(tinea pedis), ringworm (tinea capitis), jock itch (tinea cruris), tineacorporis, tinea manuum and tinea versicolor. Other dermatological fungalinfections treatable with the described biological dressings includeCandida, Epidermophyton, Microsporum, Trichophyton and Pityrosporuminfections.

Compositions for the treatment of superficial fungal infections willinclude at least one anti-fungal pharmaceutical agent. Anti-fungalagents for use in a biological dressing composition include thosewell-known in the art, such as clotrimazole (0.5% to 2.0%), ketoconazole(0.5% to 2%), econazole (1%), miconazole (2%), terconazole (0.4%),butoconazole (2%), oxiconazole (1%), sulconazole (1%), ciclopiroxolamine (1% to 8%), haloprogin (1%), tolnaftate (1%), amphotericin B(3%), butenafine (1.0%), terbinafine (0.5% to 2.0%), naftifine (0.5% to10%), nystatin and griseofulvin. References that can be consulted to aidin the selection of an appropriate pharmacological agent include Goodmanand Gilman's “The Pharmacological Basis of Therapeutics”, 9^(th)Edition, 1996, Pergamon Press, New York, and the latest edition of thePhysician's Desk Reference published by Medical Economics Company,Montvale, N.J.).

Bacterial infections that may arise can be treated simultaneously orprophylactically by additionally including a topically compatibleantibiotic pharmacological agent in the biological dressing. Antibioticmedications known in the art that will find use in preparation of thesubject compositions include clindamycin (1%), erythromycin (1.0% to2.0%), tetracycline (1% to 3%), mupirocin (2.0%), gentamicin (0.1%),metronidizole (0.75%, 1%), bacitracin (250 to 600 units/cc), neomycin(3.5 mg/cc) and polymyxin B (8,000 to 12,000 units/cc). A compositionwith a combination of antibiotics against different strains of bacteriawill be preferred for certain treatments. A steroidal pharmacologicalagent, such as betamethasone (0.025% to 0.1%), in a biological dressingintended to treat a fungal infection can additionally be included toenhance the retraction of the lesion. Biological dressings having anantibiotic medication as the primary pharmacological agent can beprepared to treat other skin disorders for which such medications aretraditionally used, including as impetigo contagiosa, acne vulgaris,other superficial skin infections of unknown etiology, andpost-operative superficial skin infections (e.g., infections that occuraround the insertion of a catheter). Wound healing can be aided andcolonization of wounds (i.e. isolated areas with first-degree burns) canbe inhibited by application of a biological dressing comprising silversulfadiazine (1%). The particular antibiotic selected to be included inthe biologic dressing will of course depend on the agents to which thestrain of bacteria causing the infection is sensitive, and the specificneeds of the patient.

A biologic dressing can also be prepared for the treatment ofsuperficial parasitic infections, such as scabies, nits and lice(including head lice and crab lice). For treating such infections,pharmacological compositions comprising miticides or pediculocides suchas crotamiton (10%) or permethrin (5%), lindane (1%), malathion (0.003%to 0.5%), benzyl benzoate (26% to 30%), thiabendazole and pyrethrins.

For treating pain associated with arthritis, joint inflammation andmuscle pain a composition of the invention can be prepared comprisingone or more resins or other film-forming agents and one or more activeingredients such as menthol (10%), methyl salicylate (10%) and capsaicin(0.01%-10%) or a corticosteriod (see below for appropriate compounds anddosages). The compositions of the invention also find use in thetreatment of dermatological inflammatory disorders, wherein the primarypharmacological agent included is a corticosteroid. Particularlycontemplated is the treatment of corticosteroid-responsive inflammatoryconditions, such as atopic dermatitis or eczema, seborrheic dermatitis,some forms of psoriasis, aphthous ulcers (canker sores), superficialskin lesions due to contact with poisonous plants such as poison oak orpoison ivy, insect bites, and other skin rashes of unknown etiology.Steroidal agents of all different grades (1-7) that are known in the artcan be included in a biological dressing preparation, such asbetamethasone (0.025% to 0.1%), clobetasol (0.05%), diflorasone (0.05%),amcinonide (0.1%), desoximetasone (0.05% to 0.25%), fluocinonide(0.05%), halsinonide (0.1%), triamcinolone (0.025% to 0.5%),hydrocortisone (0.1% to 2.5%), flurandrenolide (0.05%), alclometasone(0.05%), fluocinolone (0.01% to 0.2%), desonide (0.05%), desamethasone(0.1%) and methylprednisolone (1.0%), clocortolone (0.1%), fluticasone(0.005% to 0.05%), mometasone (0.1%), prednicarbate (0.1%), amcinonide(0.1%), and halobetasole (0.05%). The particular corticosteriodal agentselected will depend on the patient and the particular disorder beingtreated.

For the treatment of certain skin disorders, non-steroidal drugs may beappropriate. As an example, a composition comprising one or more resinsor other film-forming agents and salicylic acid (0.5% to 60%) and/orretinoic acid (Retin-A) (0.025% to 0.05%) would be suitable for thetreatment of acne, psoriasis, warts, and other hyperkeratotoicdisorders. Cantharidin (0.7%) and iniquimod (5%) are other examples ofpharmacological agents for use in a biological dressing prepared for thetreatment of warts, including genital warts. Other pharmacologicalagents suitable for the treatment of acne include tretinoin (0.025% to0.2%), isotretinoin, adapaline (0.1%), azelaic acid (20%), clindamycin,erythromycin, tetracycline, benzoyl peroxide (2.5% to 10%), andsulfacetamide (10%). A composition comprising one or more resins orother film-forming agents and metronidazole (0.75%) finds use in thetreatment of rosacea.

Biological dressings comprising anthralin (0.1% to 0.5%), calcipotriene(0.005%) and/or tazarotene find use in the treatment of psoriasis.

For certain inflammatory dermatological conditions, it may be desirableto include one or more anti-histamine compounds with a steroidalcompound in the biological dressing compositions to aid in relievingitching that is often associated with inflammatory lesions. Histamine H1and H2 receptor blockers known in the art are of use in the preparationof biologic dressings for treating certain inflammatory skin conditionsinclude the H1 blockers astemizole and terfenadine, and the H2 blockercimetidine.

Dermatological conditions which can be treated with pharmacologicalcompositions in which an anti-histamine is the primary agent includeurticaria, and itching associated with lymphoproliferative diseases suchas polycythemia rubra vera and Hodgkin's disease. Oftentimes bestresults are achieved when using both an H1 and an H2 blocker.Additionally, a medicated biologic dressing comprising the anti-pruriticdoxepin (5%) finds use in relieving the itching in patients with certaintypes of eczema. Topical doxepin appears to work by preventing theeffects of histamine.

A biologic dressing of the invention also finds use in the treatment ofsuperficial dermatological viral infections, whenever topical anti-viralmedications would be indicated. Particularly considered is theadministration of acyclovir (5%) for the treatment of viral infectionscaused by herpes (type 1 and type 2) simplex viruses, but a biologicaldressing can also be applied to superficial skin infections caused bypapillomavirus (for example, common and genital warts). Other examplesof anti-viral agents for use in a biological dressing includegancyclovir, penciclovir (1%), vidarabine (3%), idoxuridine (0.5%) andtrifluridine.

A resin-based biological dressing also finds use in providing relieffrom pain associated with the lesions caused by some dermatologicaldisorders. Particularly considered is treatment of the dermal pain thatcan be associated with varicella-zoster virus (shingles, chicken pox)with a topically compatible local anesthetic. A preferredpharmacological agent for use in a resin-based dressing prepared fortreating pain associated with dermatological disorders is lidocaine(0.5% to 25%, see U.S. Pat. Nos. 5,709,869, 5,601,838, 5,589,180 and5,411,738, incorporated herein by reference). Other local anestheticschemically and/or pharmacologically related to lidocaine, or lidocainehydrochloride, include bupivacaine hydrochloride (0.25% to 1.5%),etidocaine hydrochloride (1.0% to 3.0%), mepivacaine hydrochloride (1.0%to 5.0%), prilocaine hydrochloride (4.0% to 8.0%), and tetracainehydrochloride (0.5% to 2.0%). Other preferred local anesthetics arethose with low solubility in water, and which are particularly suitedfor sustained local anesthetic action when topically applied. Examplesof local anesthetics with low solubility in water include benzocaine andthe hydroiodide salt of tetracaine. Additional local anesthetics used intreating mucous membranes and the skin include dibucaine, dycloninehydrochloride (0.5% to 1.0%), and pramoxine hydrochloride (1.0%).Another example of a pharmacological agent used topically to relievedermatological pain includes capsaicin (0.025%).

A composition comprising one or more resins or other film-forming agentsadditionally finds use in surgical preparations for sustained release ofantiseptics. Examples of active agents suitable for use in a resin-basedbiological dressing for surgical preparations include, but are notlimited to biguanides such as chlorhexidene gluconate and alexidine,povione iodine, iodine, halogen releasing agents such as iodophor,diamidines, anilides such as triclocarban, phenols, halophenols andbis-phenols such as triclosan, peroxygens such as hydrogen peroxide,silver compounds such as silver nitrate and quarternary ammoniumcompounds.

Compositions comprising one or more resins or other film-forming agentsand containing synthetic hormones find use in the treatment ofindications associated with abnormal hormone production as well ascontraception. For example, a biologic dressing containing transdermaltestosterone, generally about 2.5-5.0 mg per application, or equivalentother androgenic compound(s) in an appropriate amount can be used totreat young males with congenital or acquired primary hypogonadism, orcongenital or acquired hypogonadotropic hypogonadism and other similardisorders. In women, a bilogic dressing containing estradiol (an activeform of estrogen) or other equivalent estrogenic compound(s) in anappropriate amount, can be used to treat the indications and symptomsassociated with atrophic vaginitis, atrophic dystrophy of the vulva,menopausal symptoms, female hypogonadism, ovariectomy, primary ovarianfailure, non-steroid dependent inoperable breast cancer and vasomotorsymptoms associated with menopause and prevention of post-menopasualosteoporosis. A biologic dressing containing an estrogenic compound,such as for example estradiol in an amount sufficient for the treatmentof such indications is used.

A composition comprising one or more resins or other film-forming agentsand containing norethindrone (progestin) can be used to preventpregnancy by inhibiting ovulation and thickening the mucosa of thecervix. In addition, a film-forming resin or other film-forming agentcomposition containing a progestin compound such as norethindrone(0.14-0.25 mg per application) can be used for treating abnormalmenstrual disorders such as amenorrhea, abnormal uterine bleeding andendometriosis, applications generally will be to the skin. The site ofapplication of the film-forming resin or other film-forming agentcomposition will vary depending upon the intended use. Generally thesite of application will be to the skin at a location that will providefor absorption into the blood stream. Particularly in the case oftreatments relating to the female genitalia, application can beintravaginally.

Film-forming resin or other film-forming agent compositions are alsosuitable for sustained delivery of pharmacological agents use for hairgrowth retardation and stimulation. For treatments intending tostimulate hair growth, compositions comprising minoxidil (1% to 5%) areprepared. For other topical formulations that can be used with the oneor more resins or other film-forming agents, see U.S. Pat. No.6,184,249. For treatment intending to retard hair growth compositionscomprising eflornithine hydrochloride (13.9%) are prepared.

A composition comprising one or more resins or other film-forming agentsadditionally finds use in preparing protective compositions comprisingone or more sun protecting, ultraviolet absorptive agents. Sunscreensfor use in a film-forming resin or other film-forming agent-baseddressing include aminobenzoate agents, such as p-aminobenzoic acid(PABA), ethyl 4-[bis(hydroxypropyl)]aminobenzoate, octyl dimethyl PABA,PABA propoxylate, glyceral PABA, 2-ethylhexyl PABA and pentyl PABA;cinnamate agents, such as cinoxate, diethanolamine-p-methoxy cinnamate,2-ethylhexyl-p-methoxycinnamate and octyl methoxycinnamate; benzones,such as oxybenzone, dioxybenzone, sulisobenzone; salicylates, such as2-ethylhexyl salicylate, triethanol amine salicylate, and octylsalicylate; and other sunscreen agents, such as meradimate (7.5%),octinoxate (7.5%), homosalate (10%), sulisobenzone (10%), titaniumdioxide and zinc oxide. For use as a sunscreen, generally a thincombination of one or more resins or other film-formingagents/ultraviolet absorptive agents is applied to areas of the skinthat will be exposed to the sun. For some situations, protection ofexposed skin from the sun will be best accomplished by applying athicker formulation of the one or more resins or other film formingagents. For example, application of sunscreen to protect the skin of thenose at high altitudes. Advantageously, a formulation comprising one ormore resins or other film-forming agents and sunscreen compound isparticularly effective at providing long-lasting sun protection toexposed skin through resisting removal by abrasion or moisture.

Compositions comprising one or more resins or other film-forming agentsmay be prepared with pharmacological agents used for pigmenting orde-pigmenting the skin, for instance, for use in treating patients withvitiligo. For treatments intending to de-pigment or lighten isolateddermal areas, a pharmacologic composition comprising hydroquinone (2% to4%) is prepared. For treatments intending to pigment desired areas ofskin, a composition comprising a psoralen agent, such as methoxalen(1.0%), for combined use with UV light, is prepared.

A medicated resin-based dressing will also find use in the sustaineddelivery of antiperspirants, anti-anginal, anti-nausea agents andanti-cancer agents. Particularly contemplated are compositionscomprising aluminum chloride (20%), for the inhibition of perspirationof isolated dermal areas, for instance to aid in carrying out surgicalprocedures. A composition comprising one or more resins or other filmforming agents and nitroglycerin (0.5% to 2.0%) will find use in thesustained transdermal delivery of this anti-anginal agent which canprovide relief from chest pains. Relief from nausea, due to motionsickness for example, can be provided using a biological dressingcomprising scopolamine. For anti-nausea purposes, a compositioncomprising one or more resins or other film-forming agents andscopolamine would be applied, behind the ear for example, before theonset of activity that potentially would induce nausea. Additionally, aresin or other film-forming agent dressing can be prepared for thesustained delivery of pharmacological agents useful in the treatment ofsuperficial cancerous and pre-cancerous lesions. Particularlycontemplated is the treatment of isolated actinic keratosis lesions witha biological dressing comprising 5-fluorouracil (5-FU; 5% to 10%).

A composition comprising one or more resins or other film-forming agentsmay also be prepared with an insect repellant as the pharmacologicagent. Examples of insect repellant compounds suitable for inclusion ina resin-based biological dressing include terpenoids, such ascitronellal, geraniol, terpentine, pennyroyal, cedarwood, eucalyptus andwintergreen; benzoquinones; aromatics, such as cresols, benzaldehyde,cinnamic aldehyde, benzoic acids; and synthetic insect repelling agents,such as N,N-diethyl-m-toluamide (DEET), ethyl hexanediol, dimethylphthalate, dimethyl ethyl hexanediol, carbate, butopyronoxyl,di-n-propyl isocinchonmeronate, N-octyl bicycloheptene, dicarboximide,and 2,3,4,5-bis(2-butylene)tetra-hydro-2-furaldehyde. For use as aninsect repellent, a resin or other film-forming agent preparation ispreferably applied as a thin coat to areas of the skin most likely to beattacked by an insect. Preferably, the insect repellant compound usedrepels insects without irritating the skin. Advantageously, as with thesunscreen preparations described above, a composition comprising one ormore resins or other film-forming agents and insect repellent isparticularly effective at providing long-lasting insect repellency onthe skin through resisting removal by abrasion or moisture.

The compositions of the invention also find use in the treatment of drugaddiction. Compositions comprising one or more resins or otherfilm-forming agents may be prepared with nicotine, generally about in anamount sufficient to decrease nicotine addition, 14-22 mg perapplication, or other amounts as appropriate, for use in the reductionand/or cessation of cigarette smoking, chewing tobacco or other nicotinecontaining compounds. The compositions are applied to the skin in alocation that provides sufficient absorption of the nicotine, typicallythe upper arm. As the need for nicotine decreases the dosage of nicotinein the composition can be adjusted downward.

Optionally, the biologic dressings of the invention may include apenetration enhancer, i.e., a chemical compound that, when included in aformulation, temporarily increases the permeability of the skin to adrug allowing more of the drug to be absorbed in a shorter period oftime. Examples of penetration enhancers that can be used includedimethylsulfoxide (DMSO), n-decyl methyl sulfoxide,N,N-dimethylacetamide, N,N-methyl-2-pyrrolidone andoctylphenylpolyethylene glycols.

The biologic dressings of the invention may also include one or moreother pharmaceutically acceptable carriers as needed that do notadversely affect the effectiveness of the drug, or the resinous deliveryvehicle and do not damage the skin to which it is applied. Suitablepharmaceutical carriers include sterile water; saline, dextrose;dextrose in water or saline; condensation products of castor oil andethylene oxide combining about 30 to about 35 moles of ethylene oxideper mole of castor oil; liquid acid; lower alkanols; oils such as cornoil; olive oil, peanut oil, sesame oil, wintergreen oil, lanolin oil andthe like, with emulsifiers such as mono- or di-glyceride of a fattyacid, or a phosphatide, e.g., lecithin, and the like; glycols;polyalkylene glycols; aqueous media in the presence of a suspendingagent, for example, sodium carboxymethyl-cellulose; sodium alginate;poly(vinyl pyrrolidone); and the like, alone, or with suitabledispensing agents such as lecithin; polyoxyethylene stearate; and thelike. The carrier may also contain adjuvants such as preserving,stabilizing, wetting, emulsifying agents and the like.

The compounds of this invention can be administered in conjunction witha transdermal patch that can include the pharmacologic agent in asuitable solvent system with the one or more film-forming agents and apolyester patch. The compounds of the present invention also can bedelivered through mucosal membranes. Transmucosal (i.e., sublingual,buccal, and vaginal) drug delivery provides for an efficient entry ofactive substances to the systemic circulation and reduces immediatemetabolism by the liver and intestinal wall flora. Transmucosal drugdosage forms are held in contact with the mucosal membrane where theydisintegrate and/or dissolve rapidly to allow immediate systemicabsorption. The method of manufacture of these formulations is known inthe art.

For aerosol administration, the pharmaceutical compositions arepreferably supplied in finely divided form together with a surfactantand propellant as pharmaceutically acceptable carriers. The surfactantis nontoxic, and preferably soluble in the propellant. Representative ofsuch agents are the esters or partial esters of fatty acids containingfrom 6 to 22 carbon atoms, such as caproic, octanoic, lauric, palmitic,stearic, linoleic, linolenic, olesteric and oleic acids with analiphatic polyhydric alcohol or its cyclic anhydride. Mixed esters, suchas mixed or natural glycerides, can be employed.

In practicing a method of treating the symptoms of a dermatologicaldisease in a patient, the pharmacological composition in its originalprepared form, is applied directly and specifically on the lesions orother damaged areas of skin requiring treatment. The biological dressingcomposition may initially be prepared in any form suitable for topicalapplication, such as a paste, a liquid, a semi-solid, a gel, asuspension, an emulsion or the like, provided that the formulationallows the one or more resins or other film-forming agents and the oneor more pharmacologically active agent to effectively adhere together tothe skin surface to which they are applied and to form a protectivebarrier over the skin once the volatile solvent has evaporated. Tominimize waste, application is generally carried out by painting orswabbing the composition at the affected site or sites, but certainpreparations can also be applied by spraying on the formulation, andallowing it to dry.

The biologic dressing composition can be applied wherever the patienthas superficial skin lesions or infections, such as on cutaneous areas,fingernails, toenails, mucous membranes, and mucocutaneous junctions(i.e., perianal, intertriginous and vulvovaginal areas). Afterapplication, the volatile solvent evaporates to leave a protectivesolidified, adherent and hydrophobic film or coating on the skin surfaceto which it has been applied. The solidified film residue comprises theone or more resins or other film-forming agents, and the one or morepharmacologically active agents. By forming a barrier holding thepharmacologically active agent or agents to the surface, the combinedfilm-forming resins or other film-forming agents permit a sustained,continuous release and a prolonged exposure to the agent or agents.Continuous exposure of the skin to the medication is maintained as longas the coating stays in place. The biologic dressing, therefore caneffect symptomatic relief with less frequent applications. For mostdermatological disorders treated using a resin or other film-formingagent-based dressing, one or two daily applications will be sufficientto promote regression or disappearance of the targeted skin lesions. Forcertain less respondent lesions, three daily applications may berequired to effect disappearance of symptoms. Other dermatologicaldisorders may require application every second day to realizesymptomatic relief. The composition conveniently can be removed at will,by application of an appropriate solvent, normally ethanol. Thecomposition can also be removed by scrubbing with soap and water.

The subject compositions can be provided for use in one or moreapplications. For treatment with a pharmaceutical composition comprisingan agent identified as one which is effective in treating the symptomsof a disease amendable to treatment by dermal application of medication,the subject compositions can be provided as kits for use in one or moredoses. The kits include containers which can also constitute a deliverysystem, holding a composition comprising an effective agent either asconcentrates (including lyophilized compositions), which may be furtherdiluted prior to use or they may be provided at the concentration ofuse, where the containers may include one or more dosages. Conveniently,in the kits single dosages can be provided in sterile containers so thatthe physician or the patient may employ the containers directly, wherethe containers have the desired amount and concentration of agents. Whenthe containers contain the formulation for direct use, usually therewill be no need for other reagents for use with the method. The kitsalso can be in the form of a transdermal or transmucosal system forsingle or multiple applications. The containers can be made of plastic,glass, metal or such material deemed appropriate for each particularmedication and can be light opaque as required for light sensitiveformulations. The containers can be color-coded, each color being uniqueto a particular product and its respective active ingredient. Thecontainers can also be color coordinated with the outer packaging tosimplify marketing and consumer purchasing. Examples of containers thatare also delivery systems are those that facilitate application of thesubject compositions to the skin or mucosa. The delivery systems can beany of a wide assortment of types of applicators (e.g. bottles), shapesand sizes of containers such as roll-on, spray with either a manual oraerosolized delivery system, applicators with small padded applicatortips for the delivery of buccal mucosal medications or syringe typeapplicators for semisolid medication such as are described in U.S. Pat.No. 5,531,703 and references cited therein, particularly for thedelivery of vaginal mucosal medications.

The subject compositions can be contained in packaging material, whichcomprises a label indicating that the subject compositions can be usedto treat dermatologic disorders in humans or to treat other disorders inhumans using transdermal delivery means.

The invention now being generally described, it will be more readilyunderstood by reference to the following examples which are included forpurposes of illustration only and are not intended to limit the presentinvention.

EXAMPLE 1 Treatment of Athlete's Foot (Tinea Pedis) with a Resin-BasedBiological Dressing Comprised of Tinture of Benzoin and Clotrimazole

Tincture of benzoin compositions are produced with standard tincture ofbenzoin (3M, Minneapolis, Minn.). Replicated experiments were performedwith a composition comprising tincture of benzoin with 90% alcohol plus1% clotrimazole. The experiments were repeated using mastic gum andelemi gum tinctures as well. To determine efficacy in treating athlete'sfoot, the benzoin/clotrimazole composition was applied to cases ofathlete's foot, replicated 5 times. In each replicate, the compositionled to complete clearance of the athlete's foot within 1 week, whenapplied twice daily for 7 days. No allergic reaction was noted in thistest, although the alcohol component reportedly led to stinging whenapplied to deep fissures. Minimal lint from the socks was noted on thecoating where the composition was applied but was easily removed withethanol. Efficacy of the benzoin/clotrimazole composition was comparedto controls of tincture of benzoin alone and no treatment. Thebenzoin/clotrimazole composition provided symptomatic relief and led tohealing more quickly than tincture of benzoin alone, though tincture ofbenzoin alone improved symptoms and signs more quickly when compared tono treatment. This is likely due to the fact that the sticky coatingfrom the tincture tends to repel moisture. Efficacy of thebenzoin/clotrimazole composition also was compared to commerciallyavailable medications such as Lamisil®, Lotrimin®, Mycelex® andTinactin®. In comparison, the benzoin/clotrimazole composition greatlydecreased the time necessary for treatment compared to formulations ofeach of the commercial medications, particularly when the commercialmedications were administered in the form of powder, liquid, solution,spray or gel. The benzoin/clotrimazole composition also decreased thetime necessary for treatment when compared to cream versions of theabove medications and was much less messy than any of the commercialpreparations tested.

EXAMPLE 2 Treatment of Onychomycosis (Tinea Unguium) with a Film-FormingResin-Based Biological Dressing Comprised of Tinture of Mastic Gum andCiclopirox

Tincture of mastic gum (Mastisol) compositions are produced withstandard Mastisol (Ferndale Laboratories in Ferndale, Mich. Replicatedexperiments were performed with a composition comprising tincture ofmastic gum with 82% alcohol plus 8% Ciclopirox. To determine efficacy intreating onychomycosis, the mastic gum/ciclopirox composition wasapplied to cases of onychomycosis, replicated 6 times. In eachreplicate, the composition led to significant improvement of theonychomycosis within 6 weeks, when applied once daily for 6 weeks. Noallergic reaction was noted in this test. Minimal lint from the sockswas noted on the coating where the composition was applied but waseasily removed with ethanol. Efficacy of the mastic gum/ciclopiroxcomposition was compared to controls of tincture of mastic gum alone andno treatment. The mastic gum/ciclopirox composition provided symptomaticrelief and led to healing more quickly than tincture of mastic gumalone, though tincture of mastic gum alone improved symptoms and signsmore quickly when compared to no treatment. This is likely due to thefact that the sticky coating from the tincture tends to repel moisture.Efficacy of the mastic gum/ciclopirox composition also was compared tocommercially available medications such as PenLac®. In comparison, themastic gum/ciclopirox composition greatly decreased the time necessaryfor treatment compared to formulations of each of the commercialmedications, particularly when the commercial medications wereadministered in the form of powder, liquid, solution, spray or gel. Themastic gum/ciclopirox composition also decreased the time necessary fortreatment when compared to cream versions of the above medications andwas much less messy than any of the commercial preparations tested.

The above results demonstrate the improved symptomatic relief from adisorder that can be achieved by administering a topically acceptablepharmacological agent in a film-forming resin carrier that forms abiological bandage in comparison presently available carriers. With afilm-forming resin-based biological dressing, relief from the unpleasantsymptoms associated with a dermatological lesion is realized moreefficiently and in a more convenient and palatable manner.

All publications and patent applications mentioned in this specificationare indicative of the level of skill of those skilled in the art towhich this invention pertains. All publications and patent applicationsare herein incorporated by reference to the same extent as if eachindividual publication or patent application was specifically andindividually indicated to be incorporate by reference.

Although the invention has been described with reference to the aboveexample, it will be understood that modifications and variations areencompassed within the spirit and scope of the invention. Accordingly,the invention is limited only by the following claims.

1. A pharmacological composition comprising: a) one or more resins; b)at least one topically acceptable pharmacologically active agent otherthan the one or more resins that is effective as a treatment forameliorating symptoms of a disease of skin or a mucous membrane of amammal, wherein the pharmacologically active agent can remain in contactwith the skin, nail or the mucous membrane for greater than 4 hourswithout toxic effects to the mammal; and c) a topically acceptablevolatile solvent for the one or more resins and the pharmacologicallyactive agent.
 2. The composition according to claim 1, wherein the oneor more resins are independently selected from the group consisting of ahard resin, an oleoresin, and a gum resin.
 3. The composition accordingto claim 2, wherein the one or more resins are selected from the groupconsisting of benzoin, mastic gum, elemi gum, and olibanum gum.
 4. Thecomposition according to claim 1, wherein the topically acceptablevolatile solvent comprises ethanol.
 5. The composition according toclaim 3, wherein the topically acceptable volatile solvent is ethanoland comprises about 60% to 95% of the composition.
 6. The compositionaccording to claim 1, wherein the pharmacologically active agent is anantimicrobial agent.
 7. The composition according to claim 6, whereinthe antimicrobial agent is an anti-fungal agent.
 8. The compositionaccording to claim 7, wherein the anti-fungal agent is clotrimazole. 9.The composition according to claim 8, wherein the clotrimazole ispresent as 1% of the composition.
 10. The composition according to claim1, wherein the pharmacologically active agent is a steroidal agent. 11.The composition according to claim 10, wherein the steroidal agent isbetamethasone.
 12. The composition according to claim 11, wherein thebetamethasone is present as 0.025-0.05% of the composition.
 13. Thecomposition according to claim 1, wherein the pharmacologically activeagent comprises both an antimicrobial agent and a steroidal agent. 14.The composition according to claim 1, further comprising a penetrationenhancer.
 15. A pharmacological composition comprising: a) one or moreresins; b) clotrimazole; and c) ethanol.
 16. The composition accordingto claim 15, wherein the one or more resins are selected from the groupconsisting of a hard resin, an oleoresin, and a gum resin.
 17. Thecomposition according to claim 16, wherein the one or more resins areselected from the group consisting of benzoin, mastic gum, elemi gum,and olibanum gum.
 18. A pharmacological composition comprising: a) oneor more resins; b) 1% clotrimazole; and c) 90% ethanol.
 19. Thecomposition according to claim 18, wherein the one or more resin areselected from the group consisting of a hard resin, an oleoresin, and agum resin.
 20. The composition according to claim 19, wherein the one ormore resins are selected from the group consisting of benzoin, masticgum, elemi gum, and olibanum gum.
 21. The composition according to claim6, wherein the antimicrobial agent is an anti-viral agent.
 22. Thecomposition according to claim 6, wherein the antimicrobial agent is anantibacterial agent.
 23. The composition according to claim 22, whereinthe antibacterial agent is an antibiotic.
 24. The composition accordingto claim 1, wherein the pharmacological agent is a hormone.
 25. Thecomposition according to claim 1, wherein the pharmacological agent isan antihistamine.
 26. The composition according to claim 7, wherein theanti-fungal agent is terbinafine.
 27. The composition according to claim26, wherein the terbinafine is present as 1% of the composition.
 28. Apharmacological composition comprising: a) one or more resins; b)terbinafine; and c) ethanol.
 29. The composition according to claim 28,wherein the one or more resins are selected from the group consisting ofa hard resin, an oleoresin, and a gum resin.
 30. The compositionaccording to claim 29, wherein the one or more resins are selected fromthe group consisting of benzoin, mastic gum, elemi gum, and olibanumgum.
 31. A pharmacological composition comprising: a) one or moreresins; b) 1% terbinafine; and c) 90% ethanol.
 32. The compositionaccording to claim 31, wherein the one or more resins are selected fromthe group consisting of a hard resin, an oleoresin, and a gum resin. 33.The composition according to claim 32, wherein the one or more resinsare selected from the group consisting of benzoin, mastic gum, elemigum, and olibanum gum.
 34. A pharmacological composition comprising: a)one or more resins; b) ciclopirox olamine; and c) ethanol.
 35. Thecomposition according to claim 34, wherein the one or more resins areselected from the group consisting of a hard resin, an oleoresin, and agum resin.
 36. The composition according to claim 35, wherein the one ormore resins are selected from the group consisting of benzoin, masticgum, elemi gum, and olibanum gum.
 37. A pharmacological compositioncomprising: a) one or more resins; b) 1% ciclopirox olamine; and c) 90%ethanol.
 38. The composition according to claim 37, wherein the one ormore resins are selected from the group consisting of a hard resin, anoleoresin, and a gum resin.
 39. The composition according to claim 38,wherein the one or more resins are selected from the group consisting ofbenzoin, mastic gum, elemi gum, and olibanum gum.
 40. The compositionaccording to claim 2, wherein the one or more resins are selected fromthe group consisting of an exudate from Burserceae trees, Eucalyptusspecies, and Myrtaceae species.
 41. The composition according to claim1, wherein the one or more resins are selected from the group consistingof an adhesive polymer, a hydrogel polymer, a cellulose bioadhesive, asynthetic lattice, and a mucosal adhesive.
 42. The composition accordingto claim 41, wherein the adhesive polymer is an acrylic polymer, apolyisobutylene, or a silicone.
 43. The composition according to claim23, wherein the antibiotic is clindamycin, erythromycin, tetracycline,mupirocin, gentamycin, metronidizole, bacitracin, neomycin, or polymyxinB.
 44. The composition according to claim 23, wherein the antibiotic isa mixture of one or more of clindamycin, erythromycin, tetracycline,mupirocin, gentamycin, metronidizole, bacitracin, neomycin, andpolymyxin B.
 45. The composition according to claim 1, furthercomprising silver sulfadiazine.
 46. The composition according to claim1, wherein the pharmacologically active agent is a miticide orpediculocide.
 47. The composition according to claim 1, wherein thepharmacologically active agent is an anesthetic.
 48. The compositionaccording to claim 1, further comprising an oil.
 49. A pharmacologicalcomposition comprising: a) one or more resins; b) naftifine; and c)ethanol.
 50. The composition according to claim 49, wherein the one ormore resins are selected from the group consisting of a hard resin, anoleoresin, and a gum resin.
 51. The composition according to claim 50,wherein the one or more resins are selected from the group consisting ofbenzoin, mastic gum, elemi gum, and olibanum gum.
 52. The compositionaccording to claim 49, further comprising a penetration enhancer. 53.The composition according to claim 52, wherein the penetration enhanceris DMSO.
 54. A pharmacological composition comprising: a) one or moreresins; b) 1% to 10% naftifine; and c) 90% ethanol. 55-56. (canceled)57. A pharmacological composition comprising: a) one or more resins; b)ciclopirox; and c) ethanol.
 58. The composition according to claim 57,wherein the one or more resins are selected from the group consisting ofa hard resin, an oleoresin, and a gum resin.
 59. The compositionaccording to claim 58, wherein the one or more resins are selected fromthe group consisting of benzoin, mastic gum, elemi gum, and olibanumgum.
 60. The composition according to claim 57, further comprising apenetration enhancer.
 61. The composition according to claim 60, whereinthe penetration enhancer is DMSO.
 62. A pharmacological compositioncomprising: a) one or more resins; b) 8% ciclopirox; and c) 90% ethanol.63. The composition according to claim 62, wherein the one or moreresins are selected from the group consisting of a hard resin, anoleoresin, and a gum resin.
 64. The composition according to claim 63,wherein the one or more resins are selected from the group consisting ofbenzoin, mastic gum, elemi gum, and olibanum gum.
 65. The compositionaccording to claim 62, further comprising a penetration enhancer. 66.The composition according to claim 62, further comprising a penetrationenhancer.
 67. A pharmacological composition comprising: a) one or moreresins; b) terbinafine; and c) ethanol.
 68. The composition according toclaim 67, wherein the one or more resins are selected from the groupconsisting of a hard resin, an oleoresin, and a gum resin.
 69. Thecomposition according to claim 68, wherein the one or more resins areselected from the group consisting of benzoin, mastic gum, elemi gum,and olibanum gum.
 70. The composition according to claim 67, furthercomprising a penetration enhancer.
 71. The composition according toclaim 70, wherein the penetration enhancer is DMSO.
 72. Apharmacological composition comprising: a) one or more resins; b)clotrimazole; and c) ethanol.
 73. The composition according to claim 72,wherein the one or more resins are selected from the group consisting ofa hard resin, an oleoresin, and a gum resin.
 74. The compositionaccording to claim 73, wherein the one or more resins are selected fromthe group consisting of benzoin, mastic gum, elemi gum, and olibanumgum.
 75. A pharmacological composition comprising: a) one or moreresins; b) Bacitracin; c) Polymysin B; and d) ethanol.
 76. Thecomposition according to claim 75, wherein the one or more resins areselected from the group consisting of a hard resin, an oleoresin, and agum resin.
 77. The composition according to claim 76, wherein the one ormore resins are selected from the group consisting of benzoin, masticgum, elemi gum, and olibanum gum.
 78. A pharmacological compositioncomprising: a) one or more resins; b) 500 units/cc Bacitracin; c) 10,000units/cc Polymyxin B; and d) 90% ethanol.
 79. A pharmacologicalcomposition comprising: a) one or more resins; b) 500 units/ccBacitracin; and c) 90% ethanol.
 80. A pharmacological compositioncomprising: a) one or more resins; b) 0.025 Retin-A; and c) 90% ethanol.81. A pharmacological composition comprising: a) one or more resins; b)0.5% to 1.8% Salicylic Acid, and c) 90% ethanol.
 82. A pharmacologicalcomposition comprising: a) one or more resins; b) 7.5% meradimate; c)7.5% octinoxate; d) 10% homosalate; e) 10% sulisobenzone; and 90%ethanol.
 83. A pharmacological composition comprising: a) one or moreresins; b) 500 units/cc Bacitracin; c) 10,000 units/cc Polymyxin B; d)3.5 mg/cc Neomycin; and e) 90% ethanol.
 84. A pharmacologicalcomposition comprising: a) one or more resins; b) 500 units/ccBacitracin; c) 3.5 mg/cc Neomycin; and d) 90% ethanol.
 85. A method oftreating a subject having onychomycosis comprising contacting a nail ofa subject having onychomycosis with a biological dressing comprising:(a) one or more resins; (b) at least one topically acceptablepharmacologically active agent other than the one or more resins that iseffective as a treatment for ameliorating symptoms of onychomycosis,wherein the pharmacologically active agent can remain in contact withthe skin or nail for greater than 4 hours without toxic effects to themammal; and c) a topically acceptable volatile solvent for the one ormore resins and the pharmacologically active agent.
 86. The method ofclaim 85, wherein the one or more resins are selected from the groupconsisting of a hard resin, an oleoresin, and a gum resin.
 87. Themethod of claim 85, wherein the one or more resins are selected from thegroup consisting of benzoin, mastic gum, elemi gum, and olibanum burn.88. The method of claim 85, wherein the pharmacologically active agentis ciclopirox, naftifine or terbinafine.
 89. The method of claim 85,wherein the solvent is ethanol, ethyl acetate, or n-propyl acetate. 90.The composition according to claim 54, further comprising a penetrationenhancer.
 91. The composition according to claim 55, wherein thepenetration enhancer is DMSO.